Prostaglandin and fatty acid ω- and (ω-1)-oxidation in rabbit lung. Acetylenic fatty acid mechanism-based inactivators as specific inhibitors

A. S. Muerhoff, D. E. Williams, N. O. Reich, C. A. CaJacob, P. R. Ortiz de Montellano, B. S.S. Masters

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Terminal acetylenic fatty acid mechanism-based inhibitors (Ortiz de Montellano, P.R., and Reich, N.O. (1984) J. Biol. Chem. 259, 4136-4141) were used as probes in determining the substrate specificity of rabbit lung cytochrome P-450 isozymes of pregnant animals in both microsomes and reconstituted systems. Lung microsomal and reconstituted P-450 form 5-catalyzed lauric acid ω- and (ω-1)-hydroxylase activities were inhibited by a 12-carbon terminal acetylenic fatty acid, 11-dodecynoic acid (11-DDYA), and an 18-carbon terminal acetylenic fatty acid, 17-octadecynoic acid (17-ODYA). Rabbit lung microsomal lauric acid ω-hydroxylase activity was more sensitive to inhibition by 11-DDYA than was (ω-1)-hydroxylase activity. In reconstituted systems containing purified P-450 form 5, both ω- and (ω-1)-hydroxylation of lauric acid were inhibited in parallel when either 11-DDYA or 17-ODYA was used. These data suggest the presence of at least two P-450 isozymes in rabbit lung microsomes capable of lauric acid ω-hydroxylation. This is the first report indicating the multiplicity of lauric acid hydroxylase in lung microsomes. Lung microsomal prostaglandin ω-hydroxylation, mediated by the pregnancy-inducible P-450(PG-ω) (Williams, D.E., Hale, S.E., Okita, R.T., and Masters, B.S.S. (1984) J. Biol. Chem. 259, 14600-14608) was subject to inhibition by 17-ODYA only, whereas 11-DDYA acid was not an effective inhibitor of this hydroxylase. We have recently developed a new terminal acetylenic fatty acid, 12-hydroxy-16-heptadecynoic acid (12-HHDYA), that contains a hydroxyl group at the ω-6 position. We show that 12-HHDYA possesses a high degree of selectivity for the inactivation of rabbit lung microsomal prostaglandin ω-hydroxylase activity which cannot be obtained with the long chain acetylenic inhibitor, 17-ODYA. In addition, 12-HHDYA has no effect on lauric acid ω- or ω-1-hydroxylation or on benzphetamine N-demethylation. The development of this new terminal acetylenic fatty acid inhibitor provides us with a useful tool with which to study the physiological role of prostaglandin ω-hydroxylation in the rabbit lung during pregnancy.

Original languageEnglish (US)
Pages (from-to)749-756
Number of pages8
JournalJournal of Biological Chemistry
Issue number2
StatePublished - 1989

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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